1. Field of the Invention
This invention relates broadly to dermal compositions for the administration of certain drugs, more specifically to amino-functional drugs, and in particular the administration of scopolamine base, from an alternative and improved polymeric matrix without the need for a membrane to control flux of the active substance.
2. Background
Scopolamine is an antiemetic popularly used to avoid nausea and vomiting as for instance occurring while traveling. The antiemetic and antinauseant properties of scopolamine and related compounds have been investigated by administering these compounds orally and intramuscularly. See, e.g., C. D. Wood and A. Graybiel, “Theory of Antimotion Sickness Drug Mechanisms,” Aerosp. Med. 43: 249-52, 1972; and C. D. Wood and A. Graybiel, “A Theory of Motion Sickness Based on Pharmacological Reactions,” Clin. Pharm. 11: 621-9, 1970; J. J. Brand and P. Whittingham, “Intramuscular Hyoscine in Control of Motion Sickness,” Lancet 2: 232-4, 1970.
Optimum drug release rate is an important factor in the prevention of nausea and vomiting accompanying motion sickness and the elimination of parasympatholytic side effects from the drug such as tachycardia, drowsiness and dry mouth. Transdermal administration of scopolamine facilitates the slow, continuous, and controlled release of the drug within the relatively narrow therapeutic window desirable for plasma levels of scopolamine without having to fear the side effects caused by overdose, such as, for example, dryness of the mouth, nausea and sensitivity to glare.
U.S. Pat. Nos. 3,797,494 and 4,031,894 describe the current commercially available product (Transderm Scop®, Novartis) which comprises scopolamine base dispersed in a gelled mixture of mineral oil and polyisobutylene, and relies upon a microporous membrane to control the dosage rate.
U.S. Pat. No. 5,714,162 describes drawbacks to the marketed scopolamine product, in particular drug instability due to crystallization, and describes transdermal delivery systems using polyacrylate adhesives having functional groups as the base polymer, and including polar inactive ingredients and a membrane to improve drug solubility and control flux.
U.S. Pat. No. 6,537,571 describes transdermal delivery systems that, in order to be able to achieve constant delivery of the active substance over the period during which such patches are usually worn (3 days), rely upon amino-resistant silicone adhesives as the base polymer in which the scopolamine is present in both crystalline and solubilized form, and also include a rate controlling membrane.
A major disadvantage with systems as described above is that they are still susceptible to drug instability. Under appropriate conditions, the active agent may remain in crystalline form given its poor solubility in the base polymer, or may recrystallize or degrade in the presence of functional groups, vinyl acetate, or polar inactive substances in the formulations.
Moreover, such systems require rate controlling membranes to achieve the appropriate drug delivery profile needed to effect therapy over the intended duration of use, adding to the cost and manufacturing burden. Membranes based on their desired copolymers with vinyl acetate may also further promote drug instability.
Thus, there remains a need for an improved dermal composition of drug carrier polymers that maintains solubilized drug stability, exhibits good adhesive and wear properties, and achieves a controllable drug flux and delivery profile for a suitable duration, such as three days, without the need for membranes, and that can be manufactured in commercially advantageous thicknesses and size.